Q2M3T9 (HYAL4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hyaluronidase-4
Short name=Hyal-4
EC=3.2.1.35

Alternative name(s):
Chondroitin sulfate endo-beta-N-acetylgalactosaminidase
Chondroitin sulfate hydrolase
Short name=CSHY
Hyaluronoglucosaminidase-4

Gene names

Name:

HYAL4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Endo-hyaluronidase that degrades hyaluronan to smaller oligosaccharide fragments. Has also chondroitin sulfate hydrolase activity, The best substrate being the galactosaminidic linkage in the sequence of a trisulfated tetrasaccharide. Ref.2 Ref.7
Catalytic activity	Random hydrolysis of (1->4)-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate.
Subcellular location	Membrane; Multi-pass membrane protein Potential.
Tissue specificity	Detected in placenta and skeletal muscle. Ref.1
Sequence similarities	Belongs to the glycosyl hydrolase 56 family.
Biophysicochemical properties	pH dependence: Optimum pH is 4.5-5 (for chondroitin sulfate hydrolase activity). Ref.2 Temperature dependence: Optimum temperature is 37 degrees Celsius.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	EGF-like domain Transmembrane Transmembrane helix
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro glycosaminoglycan catabolic process Traceable author statement Ref.1. Source: ProtInc
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	hyalurononglucosaminidase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 481	481	Hyaluronidase-4		PRO_0000301999
Regions
	Topological domain	1 – 8	8	Cytoplasmic Potential
	Transmembrane	9 – 29	21	Helical; Potential
	Topological domain	30 – 453	424	Extracellular Potential
	Transmembrane	454 – 474	21	Helical; Potential
	Topological domain	475 – 481	7	Cytoplasmic Potential
Sites
	Active site	147	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	86	1	N-linked (GlcNAc...) Potential
	Glycosylation	115	1	N-linked (GlcNAc...) Potential
	Glycosylation	343	1	N-linked (GlcNAc...) Potential
	Disulfide bond	59 ↔ 351		By similarity
	Disulfide bond	223 ↔ 237		By similarity
	Disulfide bond	376 ↔ 387		By similarity
	Disulfide bond	381 ↔ 435		By similarity
	Disulfide bond	437 ↔ 446		By similarity
Natural variations
	Natural variant	346	1	A → S. Ref.6 Corresponds to variant rs6949082 [ dbSNP | Ensembl ].		VAR_034936
Experimental info
	Sequence conflict	263	1	G → C in AAC98883. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q2M3T9 [UniParc]. Last modified September 11, 2007. Version 2. Checksum: 9D530009AA898D1F	FASTA	481	54,249
	10 20 30 40 50 60 MKVLSEGQLK LCVVQPVHLT SWLLIFFILK SISCLKPARL PIYQRKPFIA AWNAPTDQCL 70 80 90 100 110 120 IKYNLRLNLK MFPVIGSPLA KARGQNVTIF YVNRLGYYPW YTSQGVPING GLPQNISLQV 130 140 150 160 170 180 HLEKADQDIN YYIPAEDFSG LAVIDWEYWR PQWARNWNSK DVYRQKSRKL ISDMGKNVSA 190 200 210 220 230 240 TDIEYLAKVT FEESAKAFMK ETIKLGIKSR PKGLWGYYLY PDCHNYNVYA PNYSGSCPED 250 260 270 280 290 300 EVLRNNELSW LWNSSAALYP SIGVWKSLGD SENILRFSKF RVHESMRIST MTSHDYALPV 310 320 330 340 350 360 FVYTRLGYRD EPLFFLSKQD LVSTIGESAA LGAAGIVIWG DMNLTASKAN CTKVKQFVSS 370 380 390 400 410 420 DLGSYIANVT RAAEVCSLHL CRNNGRCIRK MWNAPSYLHL NPASYHIEAS EDGEFTVKGK 430 440 450 460 470 480 ASDTDLAVMA DTFSCHCYQG YEGADCREIK TADGCSGVSP SPGSLMTLCL LLLASYRSIQ L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31." Csoka A.B., Scherer S.W., Stern R. Genomics 60:356-361(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"Identification of human hyaluronidase-4 as a novel chondroitin sulfate hydrolase that preferentially cleaves the galactosaminidic linkage in the trisulfated tetrasaccharide sequence." Kaneiwa T., Mizumoto S., Sugahara K., Yamada S. Glycobiology 20:300-309(2010) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-346. Tissue: Cerebellum.
[7]	"Structures of vertebrate hyaluronidases and their unique enzymatic mechanism of hydrolysis." Jedrzejas M.J., Stern R. Proteins 61:227-238(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, 3D-STRUCTURE MODELING.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF009010 mRNA. Translation: AAC98883.1. AB470346 mRNA. Translation: BAI49593.1. AC006029 Genomic DNA. Translation: AAD43186.1. CH236947 Genomic DNA. Translation: EAL24331.1. CH471070 Genomic DNA. Translation: EAW83603.1. BC104788 mRNA. Translation: AAI04789.1. BC104790 mRNA. Translation: AAI04791.1.
IPI	IPI00099438.
RefSeq	NP_036401.2. NM_012269.2.
UniGene	Hs.28673.
3D structure databases
ProteinModelPortal	Q2M3T9.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000223026.
Protein family/group databases
CAZy	GH56. Glycoside Hydrolase Family 56.
PTM databases
PhosphoSite	Q2M3T9.
Polymorphism databases
DMDM	158564281.
Proteomic databases
PaxDb	Q2M3T9.
PRIDE	Q2M3T9.
Protocols and materials databases
DNASU	23553.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000223026; ENSP00000223026; ENSG00000106302. ENST00000476325; ENSP00000417186; ENSG00000106302.
GeneID	23553.
KEGG	hsa:23553.
UCSC	uc003vlc.3. human.
Organism-specific databases
CTD	23553.
GeneCards	GC07P123469.
H-InvDB	HIX0033519.
HGNC	HGNC:5323. HYAL4.
HPA	HPA029453.
MIM	604510. gene.
neXtProt	NX_Q2M3T9.
PharmGKB	PA29574.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77606.
HOGENOM	HOG000015133.
HOVERGEN	HBG052053.
InParanoid	Q2M3T9.
KO	K01197.
OMA	YLAKATF.
PhylomeDB	Q2M3T9.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02883-MONOMER.
Gene expression databases
ArrayExpress	Q2M3T9.
Bgee	Q2M3T9.
CleanEx	HS_HYAL4.
Genevestigator	Q2M3T9.
Family and domain databases
Gene3D	3.20.20.70. 1 hit.
InterPro	IPR013785. Aldolase_TIM. IPR000742. EG-like_dom. IPR017853. Glycoside_hydrolase_SF. IPR018155. Hyaluronidase. [Graphical view]
PANTHER	PTHR11769. PTHR11769. 1 hit.
Pfam	PF01630. Glyco_hydro_56. 1 hit. [Graphical view]
PIRSF	PIRSF038193. Hyaluronidase. 1 hit.
PRINTS	PR00846. GLHYDRLASE56.
SMART	SM00181. EGF. 1 hit. [Graphical view]
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit.
PROSITE	PS00022. EGF_1. 1 hit. PS01186. EGF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	23553.
NextBio	46112.
SOURCE	Search...

Entry information

Entry name

HYAL4_HUMAN

Accession

Primary (citable) accession number: Q2M3T9
Secondary accession number(s): D0VXG1, Q9UL99, Q9Y6T9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 11, 2007
Last sequence update:	September 11, 2007
Last modified:	May 29, 2013
This is version 73 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.